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An orthotopic mouse model for chondrosarcoma of bone provides an in vivo tool for drug testing

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Abstract

Chondrosarcoma is a malignant cartilaginous tumor of the bone. Recently, mutations in isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) were identified in central chondrosarcomas. As chondrosarcomas are notoriously resistant to conventional treatment modalities, the need for model systems to screen new treatment options is high. We used two chondrosarcoma cell lines (CH2879 and SW1353) to generate a bioluminescent orthotopic chondrosarcoma mouse model. Cell lines were stably transduced with a lentiviral luciferase expression vector, and after clonal selection, luciferase-expressing clones were subcutaneously and orthotopically implanted in nude mice. Mice injected with CH2879 cells were treated with doxorubicin over a period of 6 weeks. Both cell lines resulted in tumor growth. CH2879 tumors were consistently larger than SW1353 tumors. No difference in size could be observed between subcutaneous and orthotopic tumors. Tumor growth could be monitored over time through assessment of luciferase activity, without harming the mice. Using this model, we show that doxorubicin does not have a significant effect on in vivo tumor growth. We describe an orthotopic chondrosarcoma mouse model that can be used to test new treatment strategies evolving from in vitro research.

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Acknowledgments

The authors would like to thank Inge H. Briaire-de Bruijn, Maayke A.J.H. van Ruler, Pauline Weijers-Koster, and René Zwartbol for their technical assistance and Ben van der Geest and Fred de Boer for their assistance with the mouse experiments and caretaking. The authors are especially thankful to Dr. Erik Kaijsel for providing the vectors, Prof. Dr. Pancras C.W. Hogendoorn for the fruitful discussions, and Prof. Dr. Clemens W.G.M. Löwik for providing access to his facilities. The authors also thank the Dutch Cancer Society (UL2007-3815; UL2010-4873: J.G.v.O., J.R.M.P., D.M., M.K., and J.V.M.G.B.) for the financial support.

Conflict of interest

The authors have no competing interests to declare.

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Authors and Affiliations

  1. Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands

    Jolieke G. van Oosterwijk, Danielle Meijer & Judith V. M. G. Bovée

  2. Department of Developmental BioEngineering, University of Twente, Drienerlolaan 5, 7500AE, Enschede, The Netherlands

    Jacqueline R. M. Plass & Marcel Karperien

  3. Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands

    Ivo Que

Authors
  1. Jolieke G. van Oosterwijk
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  2. Jacqueline R. M. Plass
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  3. Danielle Meijer
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  4. Ivo Que
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  5. Marcel Karperien
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  6. Judith V. M. G. Bovée
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Corresponding author

Correspondence to Judith V. M. G. Bovée.

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Supplemental Figure S1

Injection methods. 12 mice were subcutaneously injected and 33 orthotopically, of which 7 were treated with doxorubicin. (GIF 46 kb)

High resolution image (TIFF 1249 kb)

Supplemental Figure S2

Tumor growth in the medullary cavity. Growth of chondrosarcoma tumor cells was confirmed to occur in the medullary cavity. Large tumors showed disappearance of the tibial bone and outgrowth of the tumors into the muscle tissue surrounding the tibiae (A, B: 1.73× magnification, Ai, Bi: 40× magnification showing tumor cells). (GIF 234 kb)

High resolution image (TIFF 1031 kb)

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van Oosterwijk, J.G., Plass, J.R.M., Meijer, D. et al. An orthotopic mouse model for chondrosarcoma of bone provides an in vivo tool for drug testing. Virchows Arch 466, 101–109 (2015). https://doi.org/10.1007/s00428-014-1670-y

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  • DOI: https://doi.org/10.1007/s00428-014-1670-y

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